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. 2004 Nov;41(11):801–807. doi: 10.1136/jmg.2004.022731

Clinical genetic counselling for familial cancers requires reliable data on familial cancer risks and general action plans

K Hemminki 1, C Eng 1
PMCID: PMC1735611  PMID: 15520403

Abstract

Familial cancer clustering, without obvious heritability, poses a major challenge for current cancer risk assessment and management. Reliable determination of familial risks for cancer is important for clinical genetic counselling, but medically verified data on familial risks for many malignancies have been limited. However, the nationwide Swedish Family-Cancer Database allows a reliable characterisation of familial risk for all major neoplasms. Even though alert genetic counsellors and certainly clinical cancer geneticists will consider familial cancer clustering in their purview, the standard medical referral systems, which have already been shown to be poor in capturing and referring families at high risk for heritable cancers, are unlikely to ascertain familial aggregations of other cancers that are not known to belong to an inherited cancer syndrome. The data will be helpful in implementing evidence based guidelines for helping the general medical system to ascertain and refer even familial cancer clusters to cancer genetics professionals.

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Selected References

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  1. Acheson L. S., Wiesner G. L., Zyzanski S. J., Goodwin M. A., Stange K. C. Family history-taking in community family practice: implications for genetic screening. Genet Med. 2000 May-Jun;2(3):180–185. doi: 10.1097/00125817-200005000-00004. [DOI] [PubMed] [Google Scholar]
  2. Aitken J. F., Youl P., Green A., MacLennan R., Martin N. G. Accuracy of case-reported family history of melanoma in Queensland, Australia. Melanoma Res. 1996 Aug;6(4):313–317. doi: 10.1097/00008390-199608000-00006. [DOI] [PubMed] [Google Scholar]
  3. Amir E., Evans D. G., Shenton A., Lalloo F., Moran A., Boggis C., Wilson M., Howell A. Evaluation of breast cancer risk assessment packages in the family history evaluation and screening programme. J Med Genet. 2003 Nov;40(11):807–814. doi: 10.1136/jmg.40.11.807. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Antoniou A. C., Pharoah P. D., McMullan G., Day N. E., Ponder B. A., Easton D. Evidence for further breast cancer susceptibility genes in addition to BRCA1 and BRCA2 in a population-based study. Genet Epidemiol. 2001 Jul;21(1):1–18. doi: 10.1002/gepi.1014. [DOI] [PubMed] [Google Scholar]
  5. Bondy Melissa L., Newman Lisa A. Breast cancer risk assessment models: applicability to African-American women. Cancer. 2003 Jan 1;97(1 Suppl):230–235. doi: 10.1002/cncr.11018. [DOI] [PubMed] [Google Scholar]
  6. Boyle P. Current situation of screening for cancer. Ann Oncol. 2002;13 (Suppl 4):189–198. doi: 10.1093/annonc/mdf659. [DOI] [PubMed] [Google Scholar]
  7. Burghes A. H., Vaessin H. E., de La Chapelle A. Genetics. The land between Mendelian and multifactorial inheritance. Science. 2001 Sep 21;293(5538):2213–2214. doi: 10.1126/science.1065930. [DOI] [PubMed] [Google Scholar]
  8. Burke Wylie. Genetic testing. N Engl J Med. 2002 Dec 5;347(23):1867–1875. doi: 10.1056/NEJMoa012113. [DOI] [PubMed] [Google Scholar]
  9. Carstensen B., Soll-Johanning H., Villadsen E., Søndergaard J. O., Lynge E. Familial aggregation of colorectal cancer in the general population. Int J Cancer. 1996 Nov 15;68(4):428–435. doi: 10.1002/(SICI)1097-0215(19961115)68:4<428::AID-IJC5>3.0.CO;2-2. [DOI] [PubMed] [Google Scholar]
  10. Claus E. B., Risch N. J., Thompson W. D. Age at onset as an indicator of familial risk of breast cancer. Am J Epidemiol. 1990 Jun;131(6):961–972. doi: 10.1093/oxfordjournals.aje.a115616. [DOI] [PubMed] [Google Scholar]
  11. Eerola H., Blomqvist C., Pukkala E., Pyrhönen S., Nevanlinna H. Familial breast cancer in southern Finland: how prevalent are breast cancer families and can we trust the family history reported by patients? Eur J Cancer. 2000 Jun;36(9):1143–1148. doi: 10.1016/s0959-8049(00)00093-9. [DOI] [PubMed] [Google Scholar]
  12. Eng C., Brody L. C., Wagner T. M., Devilee P., Vijg J., Szabo C., Tavtigian S. V., Nathanson K. L., Ostrander E., Frank T. S. Interpreting epidemiological research: blinded comparison of methods used to estimate the prevalence of inherited mutations in BRCA1. J Med Genet. 2001 Dec;38(12):824–833. doi: 10.1136/jmg.38.12.824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Eng C., Hampel H., de la Chapelle A. Genetic testing for cancer predisposition. Annu Rev Med. 2001;52:371–400. doi: 10.1146/annurev.med.52.1.371. [DOI] [PubMed] [Google Scholar]
  14. Fernandez E., La Vecchia C., D'Avanzo B., Negri E., Franceschi S. Family history and the risk of liver, gallbladder, and pancreatic cancer. Cancer Epidemiol Biomarkers Prev. 1994 Apr-May;3(3):209–212. [PubMed] [Google Scholar]
  15. Gail M. H., Brinton L. A., Byar D. P., Corle D. K., Green S. B., Schairer C., Mulvihill J. J. Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst. 1989 Dec 20;81(24):1879–1886. doi: 10.1093/jnci/81.24.1879. [DOI] [PubMed] [Google Scholar]
  16. Gibbs M., Stanford J. L., McIndoe R. A., Jarvik G. P., Kolb S., Goode E. L., Chakrabarti L., Schuster E. F., Buckley V. A., Miller E. L. Evidence for a rare prostate cancer-susceptibility locus at chromosome 1p36. Am J Hum Genet. 1999 Mar;64(3):776–787. doi: 10.1086/302287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Glanz K., Grove J., Le Marchand L., Gotay C. Underreporting of family history of colon cancer: correlates and implications. Cancer Epidemiol Biomarkers Prev. 1999 Jul;8(7):635–639. [PubMed] [Google Scholar]
  18. Goldgar D. E., Easton D. F., Cannon-Albright L. A., Skolnick M. H. Systematic population-based assessment of cancer risk in first-degree relatives of cancer probands. J Natl Cancer Inst. 1994 Nov 2;86(21):1600–1608. doi: 10.1093/jnci/86.21.1600. [DOI] [PubMed] [Google Scholar]
  19. Gudbjartsson Tómas, Jónasdóttir Thora J., Thoroddsen Asgeir, Einarsson Gudmundur V., Jónsdóttir Gudrún M., Kristjánsson Kristleifur, Hardarson Sverrir, Magnússon Kjartan, Gulcher Jeffrey, Stefánsson Kári. A population-based familial aggregation analysis indicates genetic contribution in a majority of renal cell carcinomas. Int J Cancer. 2002 Aug 1;100(4):476–479. doi: 10.1002/ijc.10513. [DOI] [PubMed] [Google Scholar]
  20. Hampel H., Sweet K., Westman J. A., Offit K., Eng C. Referral for cancer genetics consultation: a review and compilation of risk assessment criteria. J Med Genet. 2004 Feb;41(2):81–91. doi: 10.1136/jmg.2003.010918. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hemminki K., Dong C., Vaittinen P. Cancer risks to spouses and offspring in the Family-Cancer Database. Genet Epidemiol. 2001 Feb;20(2):247–257. doi: 10.1002/1098-2272(200102)20:2<247::AID-GEPI7>3.0.CO;2-U. [DOI] [PubMed] [Google Scholar]
  22. Hemminki K., Dong C., Vaittinen P. Familial risks in cervical cancer: is there a hereditary component? Int J Cancer. 1999 Sep 9;82(6):775–781. doi: 10.1002/(sici)1097-0215(19990909)82:6<775::aid-ijc1>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
  23. Hemminki K., Jiang Y. Cancer risks among long-standing spouses. Br J Cancer. 2002 Jun 5;86(11):1737–1740. doi: 10.1038/sj.bjc.6600302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hemminki K., Li X. Familial colorectal adenocarcinoma and hereditary nonpolyposis colorectal cancer: a nationwide epidemiological study from Sweden. Br J Cancer. 2001 Apr 6;84(7):969–974. doi: 10.1054/bjoc.2000.1718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hemminki K., Li X., Plna K., Granström C., Vaittinen P. The nation-wide Swedish family-cancer database--updated structure and familial rates. Acta Oncol. 2001;40(6):772–777. doi: 10.1080/02841860152619214. [DOI] [PubMed] [Google Scholar]
  26. Hemminki Kari, Czene Kamila. Age specific and attributable risks of familial prostate carcinoma from the family-cancer database. Cancer. 2002 Sep 15;95(6):1346–1353. doi: 10.1002/cncr.10819. [DOI] [PubMed] [Google Scholar]
  27. Hemminki Kari, Jiang Yongwen. Familial and second esophageal cancers: a nation-wide epidemiologic study from Sweden. Int J Cancer. 2002 Mar 1;98(1):106–109. doi: 10.1002/ijc.10172. [DOI] [PubMed] [Google Scholar]
  28. Hemminki Kari, Jiang Yongwen. Familial and second gastric carcinomas: a nationwide epidemiologic study from Sweden. Cancer. 2002 Feb 15;94(4):1157–1165. [PubMed] [Google Scholar]
  29. Hemminki Kari, Li Xinjun, Czene Kamila. Familial risk of cancer: data for clinical counseling and cancer genetics. Int J Cancer. 2004 Jan 1;108(1):109–114. doi: 10.1002/ijc.11478. [DOI] [PubMed] [Google Scholar]
  30. Hemminki Kari, Li Xinjun. Familial and second primary pancreatic cancers: a nationwide epidemiologic study from Sweden. Int J Cancer. 2003 Feb 10;103(4):525–530. doi: 10.1002/ijc.10863. [DOI] [PubMed] [Google Scholar]
  31. Kerber R. A., Slattery M. L. Comparison of self-reported and database-linked family history of cancer data in a case-control study. Am J Epidemiol. 1997 Aug 1;146(3):244–248. doi: 10.1093/oxfordjournals.aje.a009259. [DOI] [PubMed] [Google Scholar]
  32. King Terri M., Tong L., Pack Rebecca J., Spencer Cheri, Amos Christopher I. Accuracy of family history of cancer as reported by men with prostate cancer. Urology. 2002 Apr;59(4):546–550. doi: 10.1016/s0090-4295(01)01598-9. [DOI] [PubMed] [Google Scholar]
  33. Li Xinjun, Hemminki Kari. Familial and second lung cancers: a nation-wide epidemiologic study from Sweden. Lung Cancer. 2003 Mar;39(3):255–263. doi: 10.1016/s0169-5002(02)00535-4. [DOI] [PubMed] [Google Scholar]
  34. Lynch Henry T., de la Chapelle Albert. Hereditary colorectal cancer. N Engl J Med. 2003 Mar 6;348(10):919–932. doi: 10.1056/NEJMra012242. [DOI] [PubMed] [Google Scholar]
  35. Matikaine M. P., Pukkala E., Schleutker J., Tammela T. L., Koivisto P., Sankila R., Kallioniemi O. P. Relatives of prostate cancer patients have an increased risk of prostate and stomach cancers: a population-based, cancer registry study in Finland. Cancer Causes Control. 2001 Apr;12(3):223–230. doi: 10.1023/a:1011283123610. [DOI] [PubMed] [Google Scholar]
  36. Medalie J. H., Zyzanski S. J., Langa D., Stange K. C. The family in family practice: is it a reality? J Fam Pract. 1998 May;46(5):390–396. [PubMed] [Google Scholar]
  37. Narod S. Genetic epidemiology of prostate cancer. Biochim Biophys Acta. 1999 Jan 29;1423(1):F1–13. doi: 10.1016/s0304-419x(98)00030-4. [DOI] [PubMed] [Google Scholar]
  38. Olsson Louise, Lindblom Annika. Family history of colorectal cancer in a Sweden county. Fam Cancer. 2003;2(2):87–93. doi: 10.1023/a:1025734200635. [DOI] [PubMed] [Google Scholar]
  39. Peltonen L., McKusick V. A. Genomics and medicine. Dissecting human disease in the postgenomic era. Science. 2001 Feb 16;291(5507):1224–1229. doi: 10.1126/science.291.5507.1224. [DOI] [PubMed] [Google Scholar]
  40. Peto J., Easton D. F., Matthews F. E., Ford D., Swerdlow A. J. Cancer mortality in relatives of women with breast cancer: the OPCS Study. Office of Population Censuses and Surveys. Int J Cancer. 1996 Jan 26;65(3):275–283. doi: 10.1002/(SICI)1097-0215(19960126)65:3<275::AID-IJC1>3.0.CO;2-X. [DOI] [PubMed] [Google Scholar]
  41. Peto J., Houlston R. S. Genetics and the common cancers. Eur J Cancer. 2001 Oct;37 (Suppl 8):S88–S96. doi: 10.1016/s0959-8049(01)00255-6. [DOI] [PubMed] [Google Scholar]
  42. Pharoah Paul D. P., Antoniou Antonis, Bobrow Martin, Zimmern Ron L., Easton Douglas F., Ponder Bruce A. J. Polygenic susceptibility to breast cancer and implications for prevention. Nat Genet. 2002 Mar 4;31(1):33–36. doi: 10.1038/ng853. [DOI] [PubMed] [Google Scholar]
  43. Potter J. D. Colorectal cancer: molecules and populations. J Natl Cancer Inst. 1999 Jun 2;91(11):916–932. doi: 10.1093/jnci/91.11.916. [DOI] [PubMed] [Google Scholar]
  44. Smith Robert A., Cokkinides Vilma, von Eschenbach Andrew C., Levin Bernard, Cohen Carmel, Runowicz Carolyn D., Sener Stephen, Saslow Debbie, Eyre Harmon J., American Cancer Society American Cancer Society guidelines for the early detection of cancer. CA Cancer J Clin. 2002 Jan-Feb;52(1):8–22. doi: 10.3322/canjclin.52.1.8. [DOI] [PubMed] [Google Scholar]
  45. Sweet Kevin M., Bradley Terry L., Westman Judith A. Identification and referral of families at high risk for cancer susceptibility. J Clin Oncol. 2002 Jan 15;20(2):528–537. doi: 10.1200/JCO.2002.20.2.528. [DOI] [PubMed] [Google Scholar]
  46. Sweet Kevin M., Willis Sharla K., Ashida Sato, Westman Judith A. Use of fear-appeal techniques in the design of tailored cancer risk communication messages: implications for healthcare providers. J Clin Oncol. 2003 Sep 1;21(17):3375–3376. doi: 10.1200/JCO.2003.99.049. [DOI] [PubMed] [Google Scholar]
  47. Syngal S., Fox E. A., Eng C., Kolodner R. D., Garber J. E. Sensitivity and specificity of clinical criteria for hereditary non-polyposis colorectal cancer associated mutations in MSH2 and MLH1. J Med Genet. 2000 Sep;37(9):641–645. doi: 10.1136/jmg.37.9.641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Tyrer Jonathan, Duffy Stephen W., Cuzick Jack. A breast cancer prediction model incorporating familial and personal risk factors. Stat Med. 2004 Apr 15;23(7):1111–1130. doi: 10.1002/sim.1668. [DOI] [PubMed] [Google Scholar]
  49. Vasen H. F., Mecklin J. P., Khan P. M., Lynch H. T. The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC). Dis Colon Rectum. 1991 May;34(5):424–425. doi: 10.1007/BF02053699. [DOI] [PubMed] [Google Scholar]
  50. Wagner Anja, Barrows Alicia, Wijnen Juul Th, van der Klift Heleen, Franken Patrick F., Verkuijlen Paul, Nakagawa Hidewaki, Geugien Marjan, Jaghmohan-Changur Shantie, Breukel Cor. Molecular analysis of hereditary nonpolyposis colorectal cancer in the United States: high mutation detection rate among clinically selected families and characterization of an American founder genomic deletion of the MSH2 gene. Am J Hum Genet. 2003 Mar 25;72(5):1088–1100. doi: 10.1086/373963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Walsh P. C., Partin A. W. Family history facilitates the early diagnosis of prostate carcinoma. Cancer. 1997 Nov 1;80(9):1871–1874. doi: 10.1002/(sici)1097-0142(19971101)80:9<1871::aid-cncr28>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]
  52. Wonderling D., Hopwood P., Cull A., Douglas F., Watson M., Burn J., McPherson K. A descriptive study of UK cancer genetics services: an emerging clinical response to the new genetics. Br J Cancer. 2001 Jul 20;85(2):166–170. doi: 10.1054/bjoc.2001.1893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Yan H., Papadopoulos N., Marra G., Perrera C., Jiricny J., Boland C. R., Lynch H. T., Chadwick R. B., de la Chapelle A., Berg K. Conversion of diploidy to haploidy. Nature. 2000 Feb 17;403(6771):723–724. doi: 10.1038/35001659. [DOI] [PubMed] [Google Scholar]

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